This investigation concerns the elucidation of mechanisms involved in the pathogenesis of nutritionally-induced brain injury. Nutritional disturbances are associated with a number of nervous system disorders in humans especially children. The processes by which nutritional disturbances lead to brain injury are unknown or incompletely understood. Our studies of nutritional encephalomalacia (NE), an experimental model of nutritional brain injury in which lesions resembling infarcts occur chiefly in the cerebellum of chicks, show that vascular changes, possibly representing an incompletely defined injury of the CNS microcirculatory apparatus, precede parenchymal necrosis. The proposed study will further characterize ultrastructural and histochemical changes in brain capillaries and parenchyma during evolution of NE. The etiologic and pathogenetic significance of these changes will be determined by observing their relationships to specific dietary constituents and to the necrotic lesions. Structural changes associated with recovery of neurologic function will be characterized. The study will contribute to the understanding of CNS microcirculatory injuries resulting from lead intoxication or radiation. Information concerning the effect of tocopherol deficiency on the CNS will be obtained.